The present invention relates to methods of detecting a gas bubble in a liquid and, more particularly, to methods of detecting a gas bubble such as, for example, an air bubble, in a measuring chamber filled with a liquid, typically a specimen, quality-control or calibrating liquid, which chamber can comprise a measuring device or a sensor for determining a chemical or physical parameter of the liquid.
In the case of measuring chambers filled with liquids, especially biological liquids such as whole blood, serum, urine, etc., e.g., of blood gas analyzers, problems can occur in connection with the measurement of the specimen or during the calibration or quality control if the specimen, quality-control or calibrating agent fills the measuring chamber only incompletely, or if there are gas bubbles such as, for example, air bubbles situated in the liquid in the region of the sensors. Especially in the case of measuring chambers with small specimen volumes which can be configured in a mostly capillary manner, air bubbles will lead to faulty measurements, so that an effective verification must be carried out with respect to the presence or lack of presence of air bubbles.
Reference to the problem of enclosed air bubbles is made in U.S. Pat. No. 4,358,423, which bubbles distort the measuring result because the air bubbles prevent a sufficient wetting of the surface of the respectively used sensors. Measures which recognize such errors are especially necessary in automatically operating analyzers where the filling process of the measuring capillaries or the freedom from bubbles of the specimen material in the measuring capillaries must be checked in an automatic way. U.S. Pat. No. 4,358,423 provides a method to solve this problem in which the value of the resistance between at least two positions in the measuring chamber is measured, with the filling process of the measuring chamber being controlled depending on the determined variable of the measured resistance.
In the course of the measuring chamber there can be three contact points for the measurement of the electrical resistance, with a pair of the contacts each being used for the resistance measurement with the help of a changeover switch, i.e., either the first and second contacts or the second and third contacts are used. In a filling of the measuring chamber which contains air bubbles, the electrical contact between the first and second contacts is established first. It will be interrupted by the enclosed air bubble again before the section between the second and third contacts becomes electrically conductive. The electric signal derived therefrom can be used to interrupt the filling process and to signal a fault.
Air bubbles which only partly fill the cross section of the measuring channel or the measuring capillaries cannot be actually detected with the method described in U.S. Pat. No. 4,358,423. Although the resistance measurements would show slight differences in the measuring signal in such a case, they could not be differentiated from signal changes based on different conductivities of the individual specimens, which are caused by different hematocrit values, for example.
WO 01/33195 A1 discloses a method and an apparatus for the detection of bubbles in a liquid in which the liquid is in contact with a pO2- or a pCO2 sensor, for example. In order to verify whether a gas bubble is present in the region of the sensor, a first measured value for the gas concentration is performed at a first pressure value in the measuring chamber and thereafter the pressure is changed to a second pressure value in the measuring chamber. The gas concentration is also measured at the second pressure value and a second measured value is produced. The second measured value is compared with an expected value at the altered pressure and, depending on the difference of the two values, the presence of gas bubbles is deduced. The disadvantages in the method according to WO 01/33195 A1 are that the application is limited to the use of gas sensors. If the air bubble is situated in the region of other sensors in the measuring chamber, the same cannot be detected by this method. It is further also possible that an air bubble situated in the region of the gas sensor is pushed from the sensitive region of the electrode by the change in pressure and that as a result additional measuring components occur which distort the result of the measurement.
Finally, a device for the dynamic measurement of the bubble content of a flowing liquid is known from EP 0 484 876 B1, which comprises a device for measuring the pressure, temperature and volumetric flow rate of the liquid, with the flow rate between points of high and low pressure being measured and the bubble content of the liquid being calculated therefrom. The method substantially utilizes the change in volume of the liquid resulting from the pressure change which is dependent on the bubble content.